In this mentored patient-oriented research career development award, Lakshmi Durairaj seeks to gain expertise in clinical trials in the intensive care unit with particular emphasis on the prevention of ventilator associated pneumonia. This award will support the development of Dr. Durairaj into an independent researcher and an accomplished clinician-scientist. Drs. Joseph Zabner and James Torner will assume responsibility as the primary mentors to ensure a successful career development. The focus of this proposal is to study the effectiveness of a new intervention namely xylitol, a 5-carbon sugar, for the prevention of ventilator-associated pneumonia, a common nosocomial infection among ventilated patients. Dr. Durairaj has completed her didactic training in clinical epidemiology which also included classes in statistical methods and ethics and has a Master's degree in Epidemiology. Specific areas of career development include further training in statistical methods specific for clinical trials, design of various phases of interventional trials, data collection methods, statistical analysis and interpretation of results and planning future studies in the intensive care unit. Human airways are lined by a thin layer of liquid, which contains many antimicrobial peptides which are more potent in lower salt concentrations. Tracheal colonization is an important step in the pathogenesis of ventilator-associated pneumonia, which is an important cause of increased mortality, length of stay, and cost in the intensive care unit. Xylitol is a non-absorbable osmolyte which lowers the salt concentration of airway surface liquid and has the potential to decrease respiratory tract colonization and infection. For this proposal, Dr. Durairaj will assess airway retention time of xylitol, its effectiveness in decreasing tracheal colonization in a group of mechanically ventilated patients, and conduct a pilot safety study for prevention of this pneumonia in a randomized, double-blinded, controlled fashion. Near the termination of this award, she will submit a competitive R-01 proposal to study xylitol for prevention of ventilator-associated pneumonia. Dr. Durairaj will interface with experts in clinical research, immunology, pulmonary and critical care medicine and infectious diseases at her institution. This intellectually rich environment will help foster the career development, providing ample opportunity for critical review throughout the period of this award. Both the mentor and the institution are highly committed to Dr. Durairaj's academic success.